Chronic administration of the carcinogen, 1,2-dimethylhydrazine(DMH), to mice is known to cause cancer of the colon. These chemically induced tumors are similar in many ways to cancer of the colon in humans. The objectives of this study are: 1) to quantitate changes in the functional dynamics of crypt cells that occur early in response to DMH treatment and to determine whether or not these preneoplastic changes are reversible when treatment is terminated, and 2) to determine whether or not dietary levels of vitamin A influence the development of preneoplastic changes in epithelial cells during DMH carcinogenesis. Early changes in the crypt glands will be studied on animals which receive weekly subcutaneous injections of DMH (20 mg/kg body weight) for 1,2,4,8,12,16,20, or 25 weeks and are killed 1,3,9, or 25 weeks after the last injection. The effects of different dietary levels of vitamin A will be determined on animals given Purina laboratory chow, vitamin A-free diet, or vitamin A-supplemented diet, treated with DMH as described, and killed one week after the last injection. Controls will receive equal volumes of 0.001M EDTA. Using autoradiography after either pulse or continuous labeling with 3H-thymidine, the labeling indices of mucous and columnar cells, distribution of dividing cells in the crypt, and the rate of migration of cells in crypts will be measured in order to evaluate early disruptions in cell kinetics of crypt glands. Incorporation of 35SO4 by mucous cells will be studied after autoradiography to determine whether or not production of sulfomucins changes during transformation. Finally, DMH-induced changes in the maturity of crypt cells will be determined as measured in autoradiograms by the incorporation of 3H-leucine by crypt cells. Documentation of preneoplastic changes, evoked in crypt glands of the colon, during treatment with DMH, will provide clues to the underlying processes of tumor formation.